What alternative anticoagulants can be used in patients with impaired renal function undergoing Continuous Renal Replacement Therapy (CRRT) who have contraindications to citrate and heparin?

Alternative Anticoagulation for CRRT When Citrate and Heparin Are Contraindicated

When both citrate and heparin are contraindicated in CRRT, use direct thrombin inhibitors (argatroban preferred) or Factor Xa inhibitors (danaparoid or fondaparinux), with argatroban being the first choice in patients without severe liver failure. 1

Primary Recommendation: Direct Thrombin Inhibitors

Argatroban is the preferred alternative anticoagulant when both citrate and heparin cannot be used, particularly in patients without severe liver failure. 1

• Argatroban has less dependence on renal clearance compared to fondaparinux and rivaroxaban, making it more suitable for patients with impaired renal function 1
• In one RCT of 13 patients with end-stage renal disease receiving argatroban during hemodialysis, no thrombosis, bleeding, serious adverse events, or clinically significant changes in vital signs were reported 1
• The American Society of Hematology gives argatroban a Grade 2C recommendation for use in patients with HIT requiring renal replacement therapy who cannot receive citrate 1

Alternative Options: Factor Xa Inhibitors

Danaparoid

• Danaparoid is an acceptable alternative with less renal dependence for clearance 1
• Two RCTs comparing danaparoid to heparin in patients without HIT showed no adverse events among 62 patients receiving danaparoid 1
• Availability may be limited in some jurisdictions 1

Fondaparinux

• Fondaparinux has greater dependence on kidneys for clearance, making it less ideal in renal failure 1
• The FDA label warns that fondaparinux is substantially excreted by the kidney, and risk of adverse reactions may be greater in patients with impaired renal function 2
• A 2023 retrospective review demonstrated that fondaparinux can be used safely in kidney failure with careful anti-factor Xa monitoring, targeting peak levels of 0.6-1.3 units/mL 3
• Among 9 patients with HIT who received fondaparinux, no bleeding or other adverse events were reported 1

Bivalirudin

• Bivalirudin is another direct thrombin inhibitor option with moderate renal dependence 1
• Among 114 patients with HIT receiving bivalirudin during dialysis, 7 had new thromboembolic events and 32 died, though causality is uncertain 1

Last Resort: No Anticoagulation

If all pharmacologic anticoagulation options are contraindicated, running CRRT without anticoagulation is preferable to using heparin in patients with increased bleeding risk. 4, 5

• The KDIGO guidelines suggest regional citrate anticoagulation rather than no anticoagulation for patients with increased bleeding risk, but acknowledge that no anticoagulation may be necessary when citrate is contraindicated 1
• This approach requires accepting shorter filter lifespan and more frequent circuit changes 1

Critical Monitoring Requirements

For Argatroban

• Monitor activated clotting times or systemic aPTT to guide dosing 4, 5
• Avoid in patients with severe liver failure due to hepatic metabolism 1
• Dose adjustments are necessary based on hepatic function 1

For Fondaparinux (if used)

• Monitor anti-factor Xa activity levels, targeting 0.6-1.3 units/mL 3
• Assess renal function periodically and discontinue if severe renal impairment develops 2
• Anticoagulant effects may persist 2-4 days after discontinuation in normal renal function, and even longer in renal impairment 2
• Monitor for bleeding complications, particularly in elderly patients (≥75 years had 2.7% major bleeding rate) 2

Common Pitfalls to Avoid

• Do not use low-molecular-weight heparin as an alternative to unfractionated heparin when heparin is contraindicated—both are heparin products and share the same contraindications 1
• Do not use rivaroxaban as a first-line alternative due to very limited data and high renal dependence for clearance 1
• Ensure drug availability before planning therapy, as argatroban and danaparoid may not be available in all jurisdictions 1
• Assess liver function carefully before selecting argatroban, as severe hepatic impairment is a relative contraindication 1